1. Field Of The Invention
This invention is in the field of pharmaceutical agents which selectively act as leukotriene B.sub.4 (LTB.sub.4) antagonists.
2. Prior Art
Leukotriene D.sub.4 and C.sub.4 (LTD.sub.4 /LTC.sub.4) and leukotriene B.sub.4 (LTB.sub.4) are products of the arachidonic acid metabolic pathway. LTD.sub.4 and LTC.sub.4 are associated with smooth muscle contraction and contract guinea pig ileum, human and guinea pig bronchi and human pulmonary artery and vein. LTB.sub.4 is associated with neutrophil stimulation which is characterized by chemotaxis, aggregation and degranulation. LTB.sub.4 is believed to be an important mediator of inflammation. High levels of LTB.sub.4 are detected in rheumatoid arthritis, gout, psoriasis, and inflammatory bowel disease. Thus antagonists of LTB.sub.4 are useful in the therapy of such diseases.
Gastroenterology, 1985: 88: 580-7 discusses the role of arachidonic acid metabolites in inflammatory bowel disease.
British Medical Bulletin, (1983), vol. 39, No. 3, pp 249-254, generally discusses the pharmacology and pathophysiology of leukotriene B.sub.4.
Biochemical and Biophysical Research Communications, Vol. 138, No. 2 (1986), pp. 540-546 discusses the pharmacology of a specific LTB.sub.4 antagonist which has a different structure than compounds of this invention.
U.S. Pat. No. 4,889,871 discloses alkoxy-substituted dihydrobenzopyran-2-carboxylate derivatives which are selective antagonists of LTB.sub.4 with little or no antagonism of LTD.sub.4 and are useful as antiinflammatory agents for treating inflammatory bowel disease.